MassMassachachuusesettstts InInssttiittuutte of Technole of TechnoloogygyHaHarvarvarrd Md Meedicadicall SScchohoololBrBrigighaham am annddWWoomemenn’’s Hs HoossppitalitalVA BVA Boossttonon HeHealalthcthcaare Sre Syysstteemm2.782J/3.961J/BEH.451J/HST524J2.782J/3.961J/BEH.451J/HST524JTISSUE ENGINEERINGTISSUE ENGINEERINGIV. Stem CellsIV. Stem CellsM. SpectoM. Spectorr, Ph.D., Ph.D.Page 1CELLS FOR TISSUE ENGINEERING/CELLS FOR TISSUE ENGINEERING/REGENERATIVE MEDICINEREGENERATIVE MEDICINE••••AutologousAutologous ––Differentiated parenchymal cells of same orDifferentiated parenchymal cells of same or other tissue typeother tissue type––Undifferentiated or differentiated stem cellsUndifferentiated or differentiated stem cells (adult)(adult)AllogeneicAllogeneic––Same as aboveSame as above––Fetal stem cellsFetal stem cells––Embryonic stem cellsEmbryonic stem cellsNEED FOR STEM CELLS IN TISSUENEED FOR STEM CELLS IN TISSUE ENGINERING/ENGINERING/RREGENERATIVE MEDICINEEGENERATIVE MEDICINEProblems in UsingProblems in Using Differentiated CellsDifferentiated Cells••Limited availLimited availaabilbility of diity of difffferenerentiattiateded autologous cells.autologous cells.••MorbidiMorbidity of a hty of a haarvest prvest prrocedure anocedure anddonor site.donor site.••Limited proliferative capacity andLimited proliferative capacity and biosynbiosynththetic activity.etic activity.Page 3WHAT ARE STEM CELLS?WHAT ARE STEM CELLS?••••Cells wCells with the capacity for unlimited orith the capacity for unlimited or prolonged selfprolonged self--renewal.renewal.Cells that can produce at least one type ofCells that can produce at least one type of highly differentiated descendant.highly differentiated descendant.http://http://www.nih.gov/news/stewww.nih.gov/news/stemcell/primer.htmmcell/primer.htmNATIONAL INSTITUTES OF HEALTHNATIONAL INSTITUTES OF HEALTHMay 2000May 2000Stem Cells: A PrimerStem Cells: A Primer DefinitionsDefinitions Stem cellsStem cells--cells that have the abilitycells that have the ability to divide for indefiniteto divide for indefinite periods in culture and to give rise to speciaperiods in culture and to give rise to speciallizized cells.ed cells. ••MultMultipotentipotent--giving rise to many cell types.giving rise to many cell types.••PluripotentPluripotent--capable of giving risecapable of giving rise to most tissues of anto most tissues of an organism.organism. ••TotipotentTotipotent--having unlimited capability.having unlimited capability. TotipotentTotipotentcellcellss have the cahave the capacity to sppacity to speciaecializlize intoe intoextraextraembrembryonicyonicmembranes and tissues, the embryo, and all postembryonicmembranes and tissues, the embryo, and all postembryonic tissues and organs.tissues and organs. Page 4• Pluripotent stem cells undergo further specialization into stem cells that are committed to give rise to cells that have a particular function. These more specialized stem cells are called multipotent. • Multipotent stem cells are also found in adults. For example, the blood stem cell perform the critical role of continually replenishing our supply of blood cells . http://www.nih.gov/news/stemcell/primer.htm How are pluripotent stem cells derived?How are pluripotent stem cells derived? ••Pluripotent stemPluripotent stem cells can be isolated directlycells can be isolated directly from the inner cell mass of human embryos atfrom the inner cell mass of human embryos at thethe blastocystblastocyststage and cultured to produce astage and cultured to produce a pluripotent stem cell line.pluripotent stem cell line. ••Pluripotent stem cells can be isolated from fetalPluripotent stem cells can be isolated from fetal tissue obtained from tetissue obtained from terminrminated pregated pregnancies.nancies. Cells can be taken from the region of the fetusCells can be taken from the region of the fetus that is destined to develop into the testes or thethat is destined to develop into the testes or the ovarieovaries.s.http://www.nih.gov/news/stemcell/primer.htm Page 5http://www.nih.gov/news/stemcell/primer.htm Potential Applications of PluripotentPotential Applications of Pluripotent Stem CellsStem Cells••••••HeHelp to understand the events thlp to understand the events that occur durinat occur during development.g development. ––identificatioidentificationn of the factors involvof the factors involveed in the celld in the cell speciaspeciallizization; "decisioation; "decisionn--making" genes .making" genes .ChaChannge the way drugs are developed and tested for safety.ge the way drugs are developed and tested for safety. ––neneww medications could be initmedications could be initially tested using human cellially tested using human celllines.lines.Generation of cells and tissuGeneration of cells and tissue that could be used for soe that could be used for so--calledcalled "cell the"cell therrapies."apies." ––donated organs and tissues are often used to replace ailindonated organs and tissues are often used to replace ailinggor destroyor destroyeed tissue.d tissue.––the number of people sthe number of people suuffering froffering fromm these disthese disoorders farders farr outstrips thoutstrips the number of organs available fore number of organs available fortransplantation.transplantation. http://www.nih.gov/news/stemcell/primer.htm Adult Stem CellsAdult Stem Cells ••••Multipotent stem cells can be found in some types ofMultipotent stem cells can be found in some types of adult tissue.adult tissue. In fact, stem ceIn fact, stem cells are needed to replenishishlls are needed to replen the supply cells in our body that nothe supply cells in our body that normally wrmally weear out (ar out (e.ge.g.,., the blood stem cell).the blood stem cell). Multipotent stem cells have not been found foMultipotent stem cells have not been found for all typesr all types of adult tissue, but discoveriesof adult tissue, but discoveries in this area of reseain this area of research arerch are increasing.increasing. ––neuronal stem cells have bneuronal stem cells have been isoeen isollated from the ratated from the rat and mouse nervous systems. The experience inand mouse nervous systems. The experience in humans is more limited.humans is more limited. ––a kind of cell that may bea kind of cell that may be a neuronal stem cell hasa neuronal stem cell has been isolated from